Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer
- 4 January 2012
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 227 (1), 53-61
- https://doi.org/10.1002/path.3987
Abstract
Next‐generation sequencing is making sequence‐based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology‐pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over‐expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal‐neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate‐resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence‐based molecular pathology and personalized oncology. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Keywords
This publication has 53 references indexed in Scilit:
- deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq DataPLoS Computational Biology, 2011
- The RNA-binding protein Musashi is required intrinsically to maintain stem cell identityProceedings of the National Academy of Sciences of the United States of America, 2006
- Fibroblasts in cancerNature Reviews Cancer, 2006
- Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapiesClinical Science, 2004
- Epithelial stem cells in human prostate growth and diseaseProstate Cancer and Prostatic Diseases, 2004
- Neuroendocrine Differentiation in Hormone Refractory Prostate Cancer Following Androgen Deprivation TherapyEuropean Urology, 2004
- Hyaluronan-mediated CD44 Interaction with RhoGEF and Rho Kinase Promotes Grb2-associated Binder-1 Phosphorylation and Phosphatidylinositol 3-Kinase Signaling Leading to Cytokine (Macrophage-Colony Stimulating Factor) Production and Breast Tumor ProgressionPublished by Elsevier BV ,2003
- T-REX: reconstructing and visualizing phylogenetic trees and reticulation networksBioinformatics, 2001
- Acquisition of neuroendocrine characteristics by prostate tumor cells is reversible: implications for prostate cancer progression.1999
- Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome-positive acute lymphoblastic leukemia.Proceedings of the National Academy of Sciences of the United States of America, 1988